The impact of HER2-low status on pathological complete response and disease-free survival in early-stage breast cancer

BMC Cancer. 2024 Oct 24;24(1):1311. doi: 10.1186/s12885-024-13064-1.

Abstract

Background: The HER-2 status of breast cancer (BC) has been classified as negative or positive for a long time. Given the efficacy of novel anti-HER2-targeted antibody drug conjugates (ADCs) in HER2-low BC, a distinct subgroup of HER2-low tumors has emerged within BC. The biology and prognostic impact of HER2-low expression are not yet well defined, and inconsistent results were reported. This study aims to evaluate the impact of low HER-2 status on the response to neoadjuvant chemotherapy (NACT) and disease- free survival (DFS) rates.

Methods: We retrospectively analyzed BC patients treated with NACT from 2017 to 2023 in two cancer centers. HER2-negative patients were included. HER-2 low status was defined by IHC + 1 or + 2/ISH non-amplified, and HER2-zero was defined by IHC 0. Pathological complete response (pCR) rates and DFS between HER2-low and HER2-zero populations were compared.

Results: 170 patients were identified. 122 (72%) of these patients were HER2- zero BC, whereas 48 (28%) were HER2-low BC. Overall, pCR was achieved in 35 (20.5%) patients. Of these, pCR was observed in 30 patients (44.6%) from the HER2- zero group, compared to 5 patients (10.4%) from the HER2-low group (p = 0.046), but significance was lost in multivariate analysis. Among the hormone receptor (HR) positive subtype, pCR was achieved 19.8% of HER2-zero tumors and 7.5% of HER2-low tumors (p = 0.08). For HR-negative subtype 34.1% HER2-zero tumors had pCR and 25% of the HER2-low tumors had pCR (p = 0.614). There was no association between DFS and HER2-low status.

Conclusions: Our study indicates that HER2-low status had no impact on pCR or DFS.

Keywords: Breast cancer; HER2-low expression; Pathological complete response.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2* / metabolism
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Receptor, ErbB-2